Objective:

Studies are proposed to identify health hazards of source-specific physicochemical components of fine PM (e.g., UFP; organics) in epidemiological, controlled clinical, animal, and in vitro studies; a main focus will be on characterizing fine PM and determining pathophysiological mechanisms of effects to test the hypothesis that ambient ultrafine (UF)/fine PM cause oxidative stress and trigger cardiovascular adverse health effects, with specific emphasis on events leading to endothelial dysfunction.

Approach:

The Center is comprised of five Research Cores, representing a highly integrated approach linking measurement and physicochemical characterization of ambient ultrafine and fine PM (Core 1) with (i) epidemiological findings (Core 2) from panel studies in susceptible populations, including diabetics, MI patients and patients with genetic susceptibility; (ii) cardiovascular responses seen in controlled clinical exposures (Core 3) of healthy and diabetic subjects exposed to concentrated ambient UF/fine PM; (iii) cardiovascular effects observed in acute and subchronic studies in diabetic rats and CNS effects in a mouse model of neurodegeneration (Core 4) following exposures to concentrated ambient UF/fine PM and on-road highway aerosols; and (iv) findings from in vitro studies (Core 5) to evaluate underlying oxidative stress related mechanisms of injury that will explain in vivo findings. The Research Cores are supported by four Facility Cores: Aerosol Generation and Analysis; Vascular and Inflammation; Cardiac; and Biostatistics, which are essential elements in our coordinated research approach.

Expected Results:

We anticipate to uncover mechanisms of adverse vascular and cardiac events, directly or indirectly induced by PM. These involve activation of endothelial cells and blood platelets, resulting in thrombus formation with potential fatal consequences in susceptible subjects with predisposing cardiovascular disease. We also expect to see oxidative stress responses in the CNS at sensitive target sites. Our multidisciplinary team approach will result in novel findings to be used in regulatory decision-making for protecting public health.

Venkatachari P, Hopke PK. Development and laboratory testing of an automated monitor for the measurement of atmospheric particle-bound reactive oxygen species (ROS). Aerosol Science and Technology 2008;42(8):629-635.

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.